{"entity":{"id":"idea-bio1-glue-degrader-atlas","kind":"idea","name":"Screen glue-like compounds against every cancer cell line and publish it","aka":[],"tldr":"Molecular glue degraders make one protein destroy another, but thalidomide analogues and indisulam were found by luck. A systematic screen of chemical libraries against genetically diverse cancer cell lines, published as an open atlas, would map which of the roughly 600 human E3 ligases can be redirected and against which targets.","summary":"Molecular glue degraders (thalidomide analogues, indisulam) were discovered serendipitously. Modern discovery pairs a chemical library with degradation readouts (global proteomics, reporter panels) across genetically diverse lines, using E3 ligase knockouts to confirm mechanism. A precompetitive atlas of compound-to-degraded-protein pairs would map which of the roughly 600 human E3 ligases can be redirected and against which classes of target.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","proteomics"],"targets":[],"drugs":[],"companies":["monte-rosa","nurix","kymera","c4-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-ip-collaboration"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic glue screening at scale identifies degradation of at least 50 proteins with no known small-molecule binding site, including at least five transcription factors of oncological interest.","rationale":"Glue mechanisms do not require a target pocket, so they extend the druggable proteome to interaction surfaces. The technology is now industrialised but siloed inside a handful of companies.","test":"A funded consortium screening 100,000 compounds with proteome-wide degradation readouts across 20 lines; success measured by independently confirmed novel degraded targets released publicly.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":5},"route":"/ideas/idea-bio1-glue-degrader-atlas/","neighbours":{"technology":[{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"},{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","route":"/technologies/proteomics/"}],"company":[{"id":"c4-therapeutics","kind":"company","name":"C4 Therapeutics","route":"/companies/c4-therapeutics/"},{"id":"kymera","kind":"company","name":"Kymera Therapeutics","route":"/companies/kymera/"},{"id":"monte-rosa","kind":"company","name":"Monte Rosa Therapeutics","route":"/companies/monte-rosa/"},{"id":"nurix","kind":"company","name":"Nurix Therapeutics","route":"/companies/nurix/"}],"bottleneck":[{"id":"b-ip-collaboration","kind":"bottleneck","name":"Secrecy and intellectual property block collaboration","route":"/bottlenecks/b-ip-collaboration/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}